Establishment of novel therapy for canine degenerative myelopathy targeting SOD1 aggregates and neuroinflammation

2021 Fiscal Year Final Research Report

• Project/Area Number: 19K15978
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 42020:Veterinary medical science-related
• Research Institution: Gifu University
• Principal Investigator: Kobatake Yui 岐阜大学, 応用生物科学部, 助教 (00805442)
• Project Period (FY): 2019-04-01 – 2022-03-31
• Keywords: 犬 / 変性性脊髄症 / SOD1 / マクロファージ遊走阻止因子 / 筋萎縮性側索硬化症

Outline of Final Research Achievements

The purpose of this study was to establish a novel treatment using macrophage migration inhibitory factor (MIF) to regulate mutant SOD1 aggregate formation and neuroinflammation in canine degenerative myelopathy (DM). Using DM model cells, we clarified that the increasing intracellular MIF inhibits the formation of mutant SOD1 aggregates. We revealed that MIF was expressed in neuronal cells of the spinal cord of DM by immunohistochemistry with anti-MIF antibody. We hypothesized that the MIF secretion inhibitor suppresses the accumulation of MIF in cells and the formation of mutant SOD1 aggregates, and we conducted the experiments using DM model cells. In our study, it was not observed that accumulation of MIF and suppressing the aggregate formation by MIF secretion inhibitor.

Free Research Field

獣医神経病学

Academic Significance and Societal Importance of the Research Achievements

本研究の結果から、細胞内MIF濃度の上昇により変異型SOD1凝集体の形成が抑制されることが明らかとなった。したがって、細胞内MIF濃度を上昇させることが、変性性脊髄症の治療戦略となりうると考えられた。変性性脊髄症は筋萎縮性側索硬化症というヒトの難病の類似疾患と考えられているため、本知見は獣医療だけでなく人医療への貢献も期待できる。